It was the question that changed his life: In 1990, Mike Kaplitt was six months into his PhD program at Rockefeller University when his advisor asked him, "How would you insert a gene into a specific part of the brain?" Kaplitt off-handedly responded that he would use a virus. But that off-the-top-of-his-head idea became the seed for Kaplitt's life work. Through his New-Jersey based, gene therapy company Neurologix, which he launched in1999, he went on to complete the first successful clinical trial of gene therapy for Parkinson’s disease. Despite enormous scientific success, as a pioneer in a new field of study, Kaplitt struggled to get funding. In 2012, his company went bankrupt.

Now, Kaplitt has joined Silicon Valley-based biotech start-up, Circuit Therapeutics, with the hopes of finishing his gene therapy research. Circuit Therapeutics, a 37-person company which was founded in 2010 and is still in its preclinical stage, will build upon Kaplitt's gene therapy research and develop optogentic technologies to control neuron activity. Here, he talks with Inc.'s Abigail Tracy about running a health-tech company, getting knocked down, and getting back up.

Before we get into the business of biotech, can you tell me a little bit about gene therapy?

Sure. We often use the analogy of a Trojan horse where they used the horse to sneak soldiers into an enemy city. In gene therapy, a viral package is sneaking a gene into a cell. You don’t want anything more to happen such as producing any more viruses, so you create a very clean population of what we call vectors. A viral vector is a modified form of the virus that allows you to put a gene into the cell without creating a productive viral infection.

You founded Neurologix in 1999--what did your company do exactly?

After I first became interested in gene therapy and using viruses to deliver genes into cells, I started collaborating with two other researchers Jude Samulsky and Matt During. Jude had been working with the Adeno-associated virus (AAV), which we thought would be a great candidate for gene therapy based on the specific properties of the virus. We ran some experiments with AAV, put it in the Parkinson's model and found out it worked. Then we wrote what was our landmark paper on using AAV in the brain and it became the first viable candidate for use in human beings.

"Neurologix required investors who had a long view-- and were willing to take enough risk for a trial of this kind."

That's where Neurologix comes in. We started Neurologix because we were ready to translate our findings into human beings and thought starting a company would be the best way to do that. The purpose of Neurologix was to fund our research, studies and clinical trials so we could get our Parkinson's program approved by the FDA for use in human beings.

What was the biotech space like during that time?

This was at a time when getting funding, from the National Institutes of Health and other sources, was very difficult-- especially as gene therapy was not viewed favorably. We were out in front and were doing something that had never been done before. While that was exciting in one respect, it made it tough from an investment standpoint. Neurologix required investors who had a long view and were willing to take enough risk as we were creating all of the regulatory pathways for a trial of this kind as we went along.

In 2011, we published a successful double blind study -- the gold standard-- but the company was running out of money and was unfortunately a publicly traded company because of some decisions made at an earlier time. This was difficult because we were pushing the envelope but investments were influenced by the public stock price and Neurologix was held in limited hands. Even though we had positive results and were successful at every stage, we ran out of money and had to file bankruptcy.

You saw how hesistant investors were with your own company, so why go to another start-up now?

I was approached by Karoly Nikolich, president of Circuit Therapeutics who was involved in several Silicon Valley start-ups and had worked in the biotech space for many years. He asked me if I would be interested in working with Circuit, a company specializing in optogenetics--a form of gene therapy. This was an opportunity to take science and turn it into products.

I got so tantalizingly close with Neurologix. I was hesitant at first because I am not ready to give up neurosurgery and have had a great experience with Cornell. I wasn’t looking for a job, but the more I thought about it the more appealing it became. Now I will work in both places. I will spend my time working at the chief science officer and senior vice president at Circuit but will come back to New York to perform Parkinson’s surgeries and run my research lab.

What convinces you that this start-up will succeed where Neurologix failed?

There are a few things that set them apart, starting with timing and experience.

One of the problems with Neurologix was that it was a victim of its own success. As you are more successful with these types of trials, the more expensive studies become. We had outrun our supply lines. Its also a different world for gene therapy, because of what we did with Neurologix. People are much more accepting of putting genes into the human brain because of our work.

Circuit also has a platform technology, where with Neurologix we really only had one product which was moving along nicely, but was limited. Obviously, you must make choices. I’m not suggesting that because it’s a platform that we will do a huge number of things, but it provides Circuit with a level flexibility and makes the company more nimble. This provides a level of security.

How have funding changes with the NIH and other sources influenced funding for biotech companies and research. Has there been a move into the private space?

Let’s be honest--it’s a tougher environment to obtain government funding now. The toughest environment I have seen. For me, funding played no role in my decision to work with Circuit but I know it has influenced some. It is a very hard for people as they think about maintaining their research efforts.

Most government grants only last for a few years and the success rate is so low right now, even for the most accomplished investigators. You have to do so much to gain funding today that is hard to accomplish the work that you wanted to do.